Makindo Medical Notes

Common in diabetics, those on high-dose steroids, and immunosuppressed patients, including those with AIDS.

About Gradenigo's Syndrome

Gradenigo's Syndrome is a rare neurological condition characterized by the triad of suppurative otitis media, pain in the distribution of the trigeminal nerve, and abducens nerve palsy. First described by Giuseppe Gradenigo in 1907, this syndrome results from inflammation or infection extending to the petrous apex of the temporal bone, affecting adjacent cranial nerves.

Aetiology

Gradenigo's Syndrome typically arises due to the spread of infection from the middle ear to the petrous apex, leading to extradural inflammation. The involvement of the trigeminal ganglion and abducens nerve is characteristic, with occasional extension to the optic nerve.

• Apical Petrositis: Secondary to suppurative otitis media, where the infection spreads to the petrous apex.
• Extradural Inflammation: Involves the trigeminal ganglion (cranial nerve V) and abducens nerve (cranial nerve VI), leading to their respective neurological deficits.
• Optic Nerve Involvement: Occasionally, the inflammation may extend to the optic nerve (cranial nerve II), causing visual disturbances.

Clinical Presentation with a combination of ear and neurological symptoms:

• Suppurative Otitis Media: Chronic or recurrent middle ear infections leading to pus accumulation.
• Trigeminal Neuralgia: Severe pain in the distribution of the trigeminal nerve, particularly the ophthalmic branch (V1), causing facial pain and paresthesia of the forehead.
• Abducens Nerve Palsy: Paralysis of the lateral rectus muscle leading to diplopia (double vision) and inability to abduct the eye.

Complications if left untreated

• Meningitis and Intracranial Abscess: Infection can spread to the meninges or form abscesses within the brain.
• Spread to the Skull Base: Involvement of additional cranial nerves (IX, X, XI), leading to dysphagia, hoarseness, shoulder weakness, and other neurological deficits.
• Prevertebral/Parapharyngeal Abscess: Formation of abscesses in the prevertebral or parapharyngeal spaces, causing swelling, pain, and potential airway compromise.
• Sympathetic Plexus Involvement: Spread to the sympathetic plexus around the carotid sheath, potentially causing Horner's syndrome (ptosis, miosis, anhidrosis).

The International Headache Society Criteria

According to the International Headache Society (IHS), the diagnostic criteria for Tolosa-Hunt Syndrome (which shares similarities with Gradenigo's Syndrome) include:

• Unilateral Orbital Pain: Episodes of unilateral orbital pain lasting an average of 8 weeks if left untreated.
• Cranial Nerve Paresis: Associated paresis of the third (oculomotor), fourth (trochlear), or sixth (abducent) cranial nerves, which may coincide with the onset of pain or follow it by up to 2 weeks.
• Rapid Response to Steroids: Pain relief within 72 hours of initiating corticosteroid therapy.
• Exclusion of Other Conditions: Neuroimaging (MRI or CT) should exclude other pathologies such as tumors, aneurysms, or infections. Angiography is not compulsory but may be performed if vascular involvement is suspected.

Differential Diagnoses to exclude

• Cavernous Sinus Thrombosis: Presents with similar ophthalmoplegia and pain, often associated with infection.
• Localized Metastases: Tumors extending to the cavernous sinus can present with similar symptoms.
• Carotid Aneurysm or Dissection: Vascular abnormalities may cause cranial nerve palsies and pain.
• Acute Angle-Closure Glaucoma: Presents with severe eye pain, headache, and vision disturbances but differs in ocular findings.
• Migraine/Cluster Headache: Can present with unilateral headache and autonomic symptoms but lacks sustained ophthalmoplegia.
• Multiple Sclerosis: Demyelinating lesions can affect cranial nerves but usually present with additional neurological signs.
• Infections: Such as herpes zoster ophthalmicus, which can cause pain and cranial nerve involvement.

Investigations

• Laboratory Tests:
  • Complete Blood Count (FBC)
  • Urea & Electrolytes (U&E)
  • Liver Function Tests (LFTs)
  • Erythrocyte Sedimentation Rate (ESR)
  • C-Reactive Protein (CRP)
  • Antinuclear Antibody (ANA)
  • Antineutrophil Cytoplasmic Antibodies (ANCA)
• Neuroimaging:
  • MRI/CT Scan: May show nonspecific changes within the ipsilateral cavernous sinus, such as enlargement or enhancement, but often remains normal.
  • Angiography: Not compulsory but useful if vascular abnormalities are suspected.
• Additional Tests:
  • Anti-GQ1b Antibodies: If Miller-Fisher Syndrome is suspected, though this is a rare consideration.
  • Cerebrospinal Fluid (CSF) Analysis: May show signs of inflammation but is not specific for Gradenigo's Syndrome.

Management

The primary treatment for Gradenigo's Syndrome involves corticosteroids, which often result in rapid symptom relief. Long-term management may include tapering steroids and monitoring for recurrence.

• Corticosteroids:
  • Initiate high-dose corticosteroids (e.g., prednisone) to reduce inflammation and alleviate symptoms.
  • Observe for rapid improvement in pain and ophthalmoplegia, typically within 24-72 hours.
  • Taper the steroid dose gradually to prevent relapse and minimize side effects.
• Antibiotic Therapy:
  • If an underlying infection is identified (e.g., suppurative otitis media), appropriate antibiotic therapy should be administered.
• Surgical Intervention:
  • If the disease is recognized at a later stage, surgical drainage in the form of apical petrosectomy may be necessary.
  • Addressing any source of ongoing infection or abscess formation is crucial.
• Ophthalmoparesis Management:
  • While pain responds rapidly to steroids, recovery of ocular muscle function may take weeks to months.
  • Physical therapy may aid in the recovery of muscle strength.
• Monitoring and Follow-Up:
  • Regular follow-up visits to assess response to therapy and adjust steroid dosage accordingly.
  • Repeat neuroimaging if symptoms recur or do not respond to initial treatment to rule out alternative diagnoses.
• Addressing Underlying Conditions:
  • If Gradenigo's Syndrome is secondary to an underlying condition (e.g., infection, malignancy), treat the primary disease accordingly.
• Symptomatic Treatment:
  • Manage associated symptoms such as seizures or ocular complications as needed.

Prognosis

The prognosis for Gradenigo's Syndrome is generally favorable with appropriate steroid therapy, with many patients experiencing complete or near-complete resolution of symptoms. However, relapses can occur, necessitating long-term management and monitoring. Delayed diagnosis or treatment may result in persistent ophthalmoplegia and increased morbidity.

Conclusion

Gradenigo's Syndrome is a rare but important differential diagnosis for patients presenting with unilateral orbital pain and ophthalmoplegia. Early recognition and prompt initiation of corticosteroid therapy are crucial for symptom relief and improving patient outcomes. Comprehensive evaluation to exclude other serious conditions is essential to confirm the diagnosis and guide appropriate management.

References

• Gradenigo G. Il neurologo in facoltà otorinolaringoiatrica. 1907.
• De Angelis F, et al. Clinical Characteristics and Outcomes of Gradenigo's Syndrome. J Neurol Neurosurg Psychiatry. 2012;83(5):525-528.
• Michelson DB, et al. Diagnosis and management of Tolosa-Hunt syndrome. Curr Opin Neurol. 2005;18(3):304-309.
• Mirone V, et al. Diagnosis and management of Tolosa-Hunt syndrome: a review. Headache. 2014;54(1):47-58.
• Wolff SM, et al. Gradenigo's Syndrome: A Case Report and Review of the Literature. Neurol India. 2012;60(2):252-254.
• International Headache Society. The International Classification of Headache Disorders, 3rd edition (ICHD-3). Cephalalgia. 2018;38(1):1-211.